This project seeks answers to the questions: 1) How can the tumor-inducing selectivity of polyoma virus (Py) for a specific constellation of organs in the mouse be explained? 2) How do epithelial-mesenchymal interactions (EMI) influence the effect of Py on target epithelium? 3) How do genetic variations in Py alter tumor-site selectivity and biologic response of potential target cells? Experiments in which EMI are perturbed show that such perturbations alter the tumor phenotypes resulting from Py transformation of salivary epithelium. E.g., isozyme profiles of salivary tumors induced in vivo (unperturbed EMI) are highly constant, whereas isozyme profiles of tumors induced in salivary epithelium isolated from salivary mesenchyme are variable and differ from those of tumors induced in intact glands. Evolutionary, embryological, and genetic evidence indicates an evolutionary and developmental kinship among the epithelial organs responsive to Py. Py genetic variants have sharply differing target cell specificity. Attempts are underway to identify Py DNA segments relating to organ tropism. It is postulated that activity of a specific regulatory gene family is common to Py tumor organs and is "used" by Py to induce proliferation.